The long range goals of this project are to understand the mechanisms of action of the stem cell and undifferentiated spermatogonia in the mammalian testis; and to identify those factors which may regulate their behavior. This is of fundamental importance in male reproductive biology, since a continuing supply of spermatozoa throughout adult life ultimately depends upon the functional integrity of this spermatogonia population. Any disruption or malfunction of this compartment will have an expanding deleterious effect on the rest of the spermatogenic process. For this reason, the success of attempts to improve infertile conditions on the one hand, or to intelligently and reversibly interrupt spermatogenesis for purposes of fertility control on the other hand, require a basic understanding of stem cell behavior. Baseline experiments to characterize mechanisms of action of spermatogonia are now completed. We have seen that undifferentiated spermatogonia do alter their proliferative activities and rates of development in response to changes in hormonal environment and/or numbers of differentiating germ cells. We have begun work on our second objective, namely to search for specific regulatory factors. Initially, these studies have focused on the role of androgens in determining spermatogonial behavior. Specifically, we have used morphological, quantitative, and radioautographic tools to probe spermatogonial responses to testosterone administration in normal adult rats. We have shown that high intratesticular concentrations of testosterone are not requisite to the completion of spermatogenesis. We shall pursue this unexpected finding with a series of experiments designed to probe the interrelations between androgens, FSH, Sertoli cells, and spermatogonia. Our current postulate is that the viability of Sertoli cells and not hormones directly may be the pivotal factor in determining the viability of spermatogenesis.